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Abstract:

The present disclosure relates to a dynamic bioactive bone graft material
and a method of handling the material to prepare an implant. In one
embodiment, a method of preparing a dynamic bioactive bone graft implant
is provided. The method includes the step of providing a porous, fibrous
composition of bioactive glass fibers, wherein the fibers are
characterized by fiber diameters ranging from about 5 nanometers to about
100 micrometers, and wherein the porosity of the matrix ranges from about
100 nanometers to about 1 millimeter. The porous, fibrous composition is
introduced into a mold tray, and a shaped implant is created using the
mold tray. The composition may be wetted with a fluid such as saline or a
naturally occurring body fluid like blood prior to creating the shaped
implant. In another embodiment, the porous, fibrous composition is
provided with the mold tray as a kit.

Claims:

1. A method of preparing a dynamic bioactive bone graft implant,
comprising: providing a porous, fibrous composition of bioactive glass
fibers, wherein the fibers are characterized by fiber diameters ranging
from about 5 nanometers to about 100 micrometers, and wherein the
porosity of the matrix ranges from about 100 nanometers to about 1
millimeter; introducing the porous, fibrous composition into a mold tray;
and creating a shaped implant with the mold tray.

2. The method of claim 1, further including the step of wetting the
composition with a fluid.

3. The method of claim 2, wherein the fluid is saline.

4. The method of claim 2, wherein the fluid is a naturally occurring body
fluid.

5. The method of claim 4, wherein the fluid is blood.

6. The method of claim 1, wherein the mold tray comprises a base
component and a lid component configured to fit onto the base component
to form an enclosed container.

7. The method of claim 6, wherein the step of introducing includes
placing the porous, fibrous composition into the base component, and the
step of creating includes manually attaching the lid component to the
base component.

8. The method of claim 6, wherein the step of introducing includes
placing the porous, fibrous composition into the base component, and the
step of creating includes applying a vacuum force after attaching the lid
component to the base component.

9. The method of claim 1, further including applying force to compress
the porous, fibrous composition.

10. The method of claim 9, wherein the composition remains compressed
after the force has been removed.

11. A kit for preparing a dynamic bioactive bone graft implant,
comprising: a porous, fibrous composition of bioactive glass fibers,
wherein the fibers are characterized by fiber diameters ranging from
about 5 nanometers to about 100 micrometers, and wherein the porosity of
the matrix ranges from about 100 nanometers to about 1 millimeter; and a
mold tray including a base component and a lid component configured to
nest within the base component, each of the base and lid components
having corresponding depressed or raised portions to form a predefined
molded shape.

12. The kit of claim 11, wherein the mold tray is sterile.

13. The kit of claim 11, wherein the base component and the lid component
form an enclosed container when attached together.

14. The kit of claim 11, wherein the lid component further includes tabs
for ease of handling.

15. The kit of claim 11, wherein the mold tray is formed of a clear
material for ease of visualization.

16. The kit of claim 11, wherein the base component has more than one
preformed well for creating a shaped mold.

17. The kit of claim 11, wherein the mold tray is disposable.

18. The kit of claim 11, wherein the porous, fibrous composition has an
initial surface area greater than a well inside the base component of the
mold tray.

21. The kit of claim 11, wherein the predefined molded shape has a
tapered leading edge for ease of implantation.

Description:

CROSS-REFERENCE TO RELATED APPLICATIONS

[0001] This application claims priority to U.S. Provisional Patent
Application No. 61/389,983, filed Oct. 5, 2010, and entitled "DYNAMIC
BIOACTIVE BONE GRAFT MATERIAL AND METHODS FOR HANDLING," and to U.S.
Provisional Patent Application No. 61/256,287, filed Oct. 29, 2009, and
entitled "BONE GRAFT MATERIAL," both of which are herein incorporated by
reference in their entirety. This application is also related to
co-pending U.S. patent application Ser. No. 12/437,531, filed May 7,
2009, and entitled "DYNAMIC BIOACTIVE NANOFIBER SCAFFOLDING," which
claims priority to U.S. Provisional Application No. 61/127,172, filed on
May 12, 2008 of the same title.

FIELD

[0002] The present disclosure relates generally to bone graft materials
and methods of handling such materials. More particularly, the present
disclosure relates to a dynamic bioactive synthetic bone graft material,
and associated methods of handling the material for preparing an implant
for repairing or restoring bone tissue.

BACKGROUND

[0003] There has been a continuing need for improved bone graft materials.
Known autograft materials have acceptable physical and biological
properties and exhibit the appropriate structure for bone growth.
However, the use of autogenous bone requires the patient to undergo
multiple or extended surgeries, consequently increasing the time the
patient is under anesthesia, and leading to considerable pain, increased
risk of infection and other complications, and morbidity at the donor
site.

[0004] Alternatively, allograft devices may be used for bone grafts.
Allograft devices are processed from donor bone. Allograft devices may
have appropriate structure with the added benefit of decreased risk and
pain to the patient, but likewise incur the increased risk arising from
the potential for disease transmission and rejection. Autograft and
allograft devices are further restricted in terms of variations on shape
and size.

[0005] Unfortunately, the quality of autograft and allograft devices is
inherently variable, because such devices are made from harvested natural
materials. Likewise, autograft supplies are also limited by how much bone
may be safely extracted from the patient, and this amount may be severely
limited in the case of the seriously ill or weak.

[0006] A large variety of synthetic bone graft materials are currently
available for use. Recently, new materials, such as bioactive glass
("BAG") particulate based materials, have become an increasingly viable
alternative or supplement to natural bone- derived graft materials. These
new (non-bone derived) materials have the advantage of avoiding painful
and inherently risky harvesting procedures on patients. Also, the use of
non-bone derived materials can reduce the risk of disease transmission.
Like autograft and allograft materials, these new artificial materials
can serve as osteoconductive scaffolds that promote bone regrowth.
Preferably, the graft material is resorbable and is eventually replaced
with new bone tissue.

[0007] Many artificial bone grafts available today comprise materials that
have properties similar to natural bone, such as compositions containing
calcium phosphates. Exemplary calcium phosphate compositions contain
type-B carbonated hydroxyapatite
[Ca5(PO4)3x(CO3)x(OH)]. Calcium phosphate
ceramics have been fabricated and implanted in mammals in various forms
including, but not limited to, shaped bodies and cements. Different
stoichiometric compositions, such as hydroxyapatite (HA), tricalcium
phosphate (TCP), tetracalcium phosphate (TTCP), and other calcium
phosphate (CaP) salts and minerals have all been employed in attempts to
match the adaptability, biocompatibility, structure, and strength of
natural bone. Although calcium phosphate based materials are widely
accepted, they lack the ease of handling, flexibility and capacity to
serve as a liquid carrier/storage media necessary to be used in a wide
array of clinical applications. Calcium phosphate materials are
inherently rigid, and to facilitate handling are generally provided as
part of an admixture with a carrier material; such admixtures typically
have an active calcium phosphate ingredient to carrier ratio of about
50:50, and may have as low as 10:90.

[0008] The roles of porosity, pore size and pore size distribution in
promoting revascularization, healing, and remodeling of bone have been
recognized as important contributing factors for successful bone grafting
materials. However, currently available bone graft materials still lack
the requisite chemical and physical properties necessary for an ideal
graft material. For instance, currently available graft materials tend to
resorb too quickly, while some take too long to resorb due to the
material's chemical composition and structure. For example, certain
materials made from hydroxyapatite tend to take too long to resorb, while
materials made from calcium sulphate or B-TCP tend to resorb too quickly.
Further, if the porosity of the material is too high (e.g., around 90%),
there may not be enough base material left after resorption has taken
place to support osteoconduction. Conversely, if the porosity of the
material is too low (e.g., 30%,) then too much material must be resorbed,
leading to longer resorption rates. In addition, the excess material
means there may not be enough room left in the residual graft material
for cell infiltration. Other times, the graft materials may be too soft,
such that any kind of physical pressure exerted on them during clinical
usage causes them to lose the fluids retained by them.

[0009] Thus, there remains a need for improved bone graft materials that
provide the necessary biomaterial, structure and clinical handling
necessary for optimal bone grafting. What is also needed are dynamic bone
graft materials that provide an improved mechanism of action for bone
grafting, by allowing the new tissue formation to be achieved through a
physiologic process rather than merely from templating. There likewise
remains a need for an artificial bone graft material that can be
manufactured as required to possess varying levels of porosity, such as
nano, micro, meso, and macro porosity. Further, a need remains for a bone
graft material that can be selectively composed and structured to have
differential or staged resorption capacity, while providing material than
can be easily molded or shaped into clinically relevant shapes as needed
for different surgical and anatomical applications. In particular, it
would be highly desirable to provide a bone graft material that includes
the characteristics of variable degrees of porosity, differential
bioresorbability, compression resistance and radiopacity, and also
maximizes the content of active ingredient relative to carrier materials
such as collagen. Even more desirable would be a bone graft material that
possesses all of the advantages mentioned above, and includes
antimicrobial properties as well as allowing for drug delivery that can
be easily handled in clinical settings. Embodiments of the present
disclosure address these and other needs.

SUMMARY

[0010] The present disclosure provides bioactive bone graft materials and
methods for handling the bone graft materials. These graft materials are
dynamic and accordingly can be molded and shaped as desired. These bone
graft materials address the unmet needs aforementioned by providing the
necessary biomaterial, structure and clinical handling for optimal bone
grafting. In addition, these bone graft materials provide an improved
mechanism of action for bone grafting, by allowing the new tissue
formation to be achieved through a physiologic process of induction and
formation rather than merely from templating and replacement. Further,
these artificial bone graft materials can be manufactured as required to
possess varying levels of porosity, such as nano, micro, meso, and macro
porosity. The bone graft materials can be selectively composed and
structured to have differential or staged resorption capacity, while
being easily molded or shaped into clinically relevant shapes as needed
for different surgical and anatomical applications. Additionally, these
bone graft materials may have variable degrees of porosity, differential
bioresorbability, compression resistance and radiopacity, and can also
maximize the content of active ingredient relative to carrier materials
such as collagen. These bone graft materials also possess antimicrobial
properties as well as allows for drug delivery. The materials can also be
easily handled in clinical settings.

[0011] In one embodiment, a method of preparing a dynamic bioactive bone
graft implant is provided. The method includes the step of providing a
porous, fibrous composition of bioactive glass fibers, wherein the fibers
are characterized by fiber diameters ranging from about 5 nanometers to
about 100 micrometers, and wherein the porosity of the matrix ranges from
about 100 nanometers to about 1 millimeter. The porous, fibrous
composition is introduced into a mold tray, and a shaped implant is
created with the mold tray. The composition may be wetted with a fluid
such as saline or a naturally occurring body fluid like blood prior to
creating the shaped implant.

[0012] The mold tray may comprise a base component and a lid component
configured to fit onto the base component to form an enclosed container.
The implant may be created using applied force such as manual pressure,
or vacuum pressure. For example, the force may be from simply filling the
mold tray with the material. In one embodiment, the applied force
compresses the porous, fibrous composition. The composition may remain
compressed after the force has been removed.

[0013] In another embodiment, a kit for preparing a dynamic bioactive bone
graft implant is provided. The kit includes a porous, fibrous composition
of bioactive glass fibers, wherein the fibers are characterized by fiber
diameters ranging from about 5 nanometers to about 100 micrometers, and
wherein the porosity of the matrix ranges from about 100 nanometers to
about 1 millimeter. The kit also includes a mold tray having a base
component and a lid component configured to nest within the base
component. Each of the base and lid components may have corresponding
depressed or raised portions to form a predefined molded shape.

[0014] The mold tray may be sterile. In addition, the base component and
lid component form an enclosed container when attached together. The lid
component may further include tabs for ease of handling. The base
component may have more than one preformed well for creating a shaped
mold. Accordingly, more than one shape may be created with the same mold
tray. That shape may be, for example, a rectangle, square, disc,
crescent, star, wave, diamond, C-shape, W-shape, S-shape, or T-shape.
Further, the predefined molded shape may have rounded edges to create a
smooth implant. Alternatively, the predefined molded shape may have a
tapered leading edge for ease of implantation. The molded tray may be
disposable.

BRIEF DESCRIPTION OF THE DRAWINGS

[0015] The foregoing and other features of the present disclosure will
become apparent to one skilled in the art to which the present disclosure
relates upon consideration of the following description of exemplary
embodiments with reference to the accompanying drawings. In the Figures:

[0016] FIG. 1A is an illustration of a dynamic fibrous bioactive glass
matrix according to a first embodiment of the present disclosure.

[0017] FIG. 1B is an enlarged view of the matrix of FIG. 1A.

[0018] FIG. 2A is a perspective view of a first interlocking, entangled
porous construct formed of the fibrous bioactive glass matrix of FIG. 1.

[0019] FIG. 2B is a perspective view of a second interlocking, entangled
porous construct formed of the fibrous bioactive glass matrix of FIG. 1.

[0020] FIG. 2C is a perspective view of a third interlocking, entangled
porous construct formed of the fibrous bioactive glass matrix of FIG. 1.

[0021] FIG. 3A is an illustration of a dynamic bioactive glass matrix
having both fibers and particulate according to another embodiment of the
present disclosure.

[0022] FIG. 3B is an enlarged view of the matrix of FIG. 3A.

[0023] FIG. 4A is an illustration of an exemplary bioactive glass fiber
bone graft material according to the present disclosure having an
organized parallel fiber arrangement with descending layers of fibers in
cross-directional relationship to alternating layers of fibers.

[0025] FIG. 4C is an illustration of an exemplary bioactive glass fiber
bone graft material constructed as a mesh with descending layers of
fibers being arranged so as to have a different degree of porosity
relative to the previous layer of fibers, thus providing a cell filter
functionality.

[0026] FIG. 5A is a perspective view of a packaging container according to
a medical kit embodiment of the present disclosure.

[0027] FIG. 5B is a perspective view of the embodiment of FIG. 5A
including fibrous bioactive bone graft material positioned in the kit.

[0028] FIG. 5C is a perspective view of the bone graft material of FIG. 5B
removed from the kit.

[0029] FIGS. 6A-6D show different embodiments of a packaging container and
mold tray according to the present disclosure.

[0030] FIGS. 7A-7L illustrate various methods for creating a shaped or
molded bone graft material in accordance with the present disclosure.

DETAILED DESCRIPTION OF THE EMBODIMENTS

[0031] The standard method for healing natural tissue with synthetic
materials has been to provide a device having the microstructure and
macrostructure of the desired end product. Where the desired end product
is cancellous bone, traditional bone grafts have been engineered to mimic
the architecture of cancellous bone. Although this has been the current
standard for bone grafts, it does not take into account the fact that
bone is a living tissue. Each bony trabeculae is constantly undergoing
active biologic remodeling in response to load, stress and/or damage. In
addition, cancellous and cortical bone also support a vast network of
vasculature. This network not only delivers nutrients to sustain the
living environment surrounding bone, but also supports red blood cells
and marrow required for basic biologic function. Therefore, merely
providing a synthetic material with the same architecture that is
non-biologic is insufficient for optimal bone healing and bone health.
Instead, what is required is a mechanism that can recreate the living
structure of bone.

[0032] Traditional synthetics act as a cast, or template, for normal bone
tissue to organize and form. Since these synthetics are not naturally
occurring, eventually the casts or templates have to be resorbed to allow
for normal bone to be developed. If these architectured synthetics do not
resorb and do not allow proper bone healing, they simply become foreign
bodies that are not only obstacles, but potentially detrimental, to bone
healing. This phenomenon has been observed in many studies with slow
resorbing or non-resorbing synthetics. Since these synthetics are just
inert, non-biologic structures that only resemble bone, they behave as a
mechanical block to normal bone healing and development.

[0033] With the understanding that bone is a living biologic tissue and
that inert structures will only impede bone healing, a different
physiologic approach is presented with the present invention. Healing is
a phasic process starting with some initial reaction. Each phase builds
on the reaction that occurred in the prior phase. Only after a cascade of
phases does the final development of the end product occur--bone. The
traditional method has been to replace or somehow stimulate healing by
placing an inert final product as a catalyst to the healing process. This
premature act certainly does not account for the physiologic process of
bone development and healing.

[0034] The physiologic process of bone healing can be broken down to three
phases: (a) inflammation; (b) osteogenesis; and (c) remodeling.
Inflammation is the first reaction to injury and a natural catalyst by
providing the chemotactic factors that will initiate the healing process.
Osteogenesis is the next phase where osteoblasts respond and start
creating osteoid, the basic material of bone. Remodeling is the final
phase in which osteoclasts and osteocytes then recreate the
three-dimensional architecture of bone.

[0035] In a normal tissue repair process, at the initial phase a fibrin
clot is made that provides a fibrous architecture for cells to adhere.
This is the cornerstone of all connective tissue healing. It is this
fibrous architecture that allows for direct cell attachment and
connectivity between cells. Ultimately, the goal is to stimulate cell
proliferation and osteogenesis in the early healing phase and then allow
for physiologic remodeling to take place. Since the desired end product
is a living tissue and not an inert scaffold, the primary objective is to
stimulate as much living bone as possible by enhancing the natural fiber
network involved in initiation and osteogenesis.

[0036] The bone graft material of the present disclosure attempts to
recapitulate the normal physiologic healing process by presenting the
fibrous structure of the fibrin clot. Since this bioactive material made
of fibers is both osteoconductive as well as osteostimulative, this
fibrous network will further enhance and accelerate bone induction.
Further, the dynamic nature of the bioactive fibrous matrix or scaffold
allows for natural initiation and stimulation of bone formation rather
than placing a non-biologic template that may impede final formation as
with current graft materials. The fibers of the present material can also
be engineered to provide a chemical reaction known to selectively
stimulate osteoblast proliferation or other cellular phenotypes.

[0037] The present disclosure provides bone graft materials and bone graft
implants formed from these materials. These bone graft materials provide
the necessary biomaterial, structure and clinical handling for optimal
bone grafting. In addition, these bone graft materials provide an
improved mechanism of action for bone grafting, by allowing the new
tissue formation to be achieved through a physiologic process rather than
merely from templating. Further, these artificial bone graft materials
can be manufactured as required to possess varying levels of porosity,
such as nano, micro, meso, and macro porosity. The bone graft materials
can be selectively composed and structured to have differential or staged
resorption capacity, while being easily molded or shaped into clinically
relevant shapes as needed for different surgical and anatomical
applications. Additionally, these bone graft materials may have variable
degrees of porosity, differential bioresorbability, compression
resistance and radiopacity, and can also maximize the content of active
ingredient relative to carrier materials such as collagen. These bone
graft materials also possess antimicrobial properties as well as allows
for drug delivery. The materials can also be easily handled in clinical
settings, and can be provided in kits that allow for a hands-free,
controlled environment for manipulating the material.

[0038] Embodiments of the present disclosure may employ a dynamic,
ultraporous bone graft material, for example, having nano, micro, meso
and macro porosities. The bone graft material can comprise bioactive
("BAG") fibers or a combination of BAG fibers and particulates of
materials. The bone graft material is a dynamic structure that can be
molded or packed into a desired shape. The bone graft material may be
osteoconductive and/or osteostimulatory. By varying the diameter and
chemical composition of the components used in the embodiments, the bone
graft material may have differential activation (i.e., resorbability),
which may facilitate advanced functions like drug delivery including
antibiotics. Furthermore, the fibrous nature of the bone graft material
helps facilitate in situ catalytic conversion of fibrinogen to fibrin by
thrombin to form cross-linked fibrin clots or matrix, thereby providing
fiber mediated healing which is essential for any kind of connective
tissue healing.

[0039] The embodiments of the bone graft material can include BAG fibers
having a relatively small diameter, and in particular, a diameter less
than 100 nanometers. In one embodiment, the fiber diameter can be less
than 10 nanometers, and in another embodiment, the fiber diameter can be
in the range of about 5 nanometers. Since the materials used in the
embodiments are bioactive materials, the bone graft material may form a
CaP layer on its surface when it interacts with body fluids.

[0040] In other embodiments, the bone graft material may comprise
particulates in combination with fibers. The presence of particulate
matter may be employed to modify or control the resorption rate and
resorption profile of the bone graft material as well as provide
mechanical strength and compression resistance. The particulate may be
bioactive glass, calcium sulfate, calcium phosphate or hydroxyapatite.
The particulate may be solid, or it may be porous.

[0041] The bone graft material may be moldable and can be packaged in
functional molds for convenient clinical handling. In addition, the bone
graft material can be mixed with other additives like collagen, etc., for
example, to further facilitate handling. The bone graft material and
collagen composite may be in the form of a foam, and the foam may
additionally be shaped into a strip, a continuous rolled sheet, a sponge
or a plug. However, it is understood that the foam may take any
configuration with any variety of shapes and sizes. In addition, the bone
graft material and collagen composite may take the form of a putty or
other moldable material. For example, in one embodiment, the BAG fibers
and particulates may be mixed with a slurry of collagen, poured into a
mold of a desired shape, and frozen to yield a desire foam shape. In
another example depending upon the type of collaged used, the foam can
have a fixed shape or the foam may be turned into a putty with the
addition of fluids such as saline, blood or bone marrow aspirate.
Alternatively, the bone graft material may be in the form of an
injectable material.

[0042] Putties can be made by combining the bone graft material with other
additives such as CMC, hyaluronic acid, or sodium alginate, for instance.
The ability to provide a bone graft material in the form of a putty
renders the material easily usable, since the putty may be applied
directly to the injury site by either injection or by plastering. Also,
the ease of handling and moldability of the putty composition allows the
clinician to form the material easily and quickly into any desired shape.

[0043] Reference will now be made to the embodiments illustrated in the
drawings. It will nevertheless be understood that no limitation of the
scope of the present disclosure is thereby intended, with such
alterations and further modifications in the illustrated device and such
further applications of the principles of the present disclosure as
illustrated therein being contemplated as would normally occur to one
skilled in the art to which the present disclosure relates.

[0044] The present disclosure relates to a synthetic bone graft material
that can be manufactured in a wide variety of compositional and
structural forms for the purpose of introducing a biocompatible,
bioabsorbable structural matrix in the form of an implant for the repair
or treatment of bone. The bone graft material can be an osteostimulative
and/or osteoconductive implant having differential bioabsorbability. In
some embodiments, the bone graft material may be substantially comprised
of BAG fibers.

[0045] In one embodiment, the bone graft material can be selectively
determined by controlling compositional and manufacturing variables, such
as bioactive glass fiber diameter, size, shape, and surface
characteristics as well as the amount of bioactive glass particulate
content and structural characteristics, and the inclusion of additional
additives, such as, for example tricalcium phosphate, hydroxyapatite, and
the like. By selectively controlling such manufacturing variables, it is
possible to provide an artificial bone graft material having selectable
degrees of characteristics such as porosity, bioabsorbability, tissue
and/or cell penetration, calcium bioavailability, flexibility, strength,
compressibility and the like. These and other characteristics of the
disclosed bone graft material are discussed in greater detail below.

[0046] The bioactive glass used in the bone graft material may have a
composition similar to 45S5 (46.1 mol % SiO2, 26.9 mol % CaO, 24.4
mol % Na2O and 2.5 mol % P2O5, 58S (60 mol % SiO2, 36
mol % CaO and 4 mol % P2O5), S70C30 (70 mol % SiO2, 30 mol
% CaO), and the like. Of course, bioactive glasses that are silicon free
may also be employed. For example, bioactive glass compositions that are
SiO2 free, and having boron instead of silicon, may also be used.
The bone graft material may be tailored to have specific desired
characteristics, such as increased X-ray opacity (for example, by
incorporating strontium), slower or faster dissolution rate in vivo,
surface texturing, or the like.

[0047] The bone graft material may serve as a scaffold for bone activity
in the bone defect. The scaffolding materials used in the bone graft may
be bioactive glasses, such as 45S5 glass, which can be both
osteoconductive and osteostimulatory. As determined by applicants, the
bioactive glass may have naturally inherent antimicrobial properties due
to the presence of sodium in the material's composition. The extensive
surface area provided by the present fibrous bone graft material allows
for antimicrobial benefits with the use of this material.

[0048] Bone graft materials of the present disclosure can be flexible,
moldable, or can be preformed to mimic, augment or replace specific
shaped structures. For example, the bone graft materials can be formed
into acetabulum cups and other skeletal modeled components employed in
surgical procedures. The bone graft materials can be formed into any
clinically useful shape, such as strips, blocks, wedges, and the like.
The shapes may be formed by molding, as will be described in greater
detail below, or simply by cutting, tearing, folding, or separating the
fibrous material into the desired configuration for its clinical
application

[0049] In the embodiments, the bone graft material is formed from
bioactive glass fibers, which may be manufactured having predetermined
cross-sectional diameters sized as desired. The fibers may be formed by
electro spinning or laser spinning, for instance, to create consistently
uniform fibers. In one embodiment, the bone graft material may be formed
from a scaffold of fibers of uniform diameters. Further, the bioactive
glass fibers may be formed having varying diameters and/or
cross-sectional shapes, and may even be drawn as hollow tubes.
Additionally, the fibers may be meshed, woven, intertangled and the like
for provision into a wide variety of shapes.

[0050] For example, a bioactive glass fiber bone graft material
manufactured such that each fiber is juxtaposed or out of alignment with
the other fibers could result in a bone graft material having a
glass-wool or "cotton-ball" appearance due to the large amount of empty
space created by the random relationship of the individual glass fibers
within the material. Such a manufacture enables a bone graft material
with an overall soft or pliable texture so as to permit the surgeon to
manually form the material into any desired overall shape to meet the
surgical or anatomical requirements of a specific patient's surgical
procedure. Such material also easily lends itself to incorporating
additives randomly dispersed throughout the overall bone graft material,
such as included bioactive glass particles, antimicrobial fibers,
particulate medicines, trace elements or metals such as copper, which is
a highly angiogenic metal, strontium, magnesium, zinc, etc. mineralogical
calcium sources, and the like. Further, the bioactive glass fibers may
also be coated with organic acids (such as formic acid, hyaluronic acid,
or the like), mineralogical calcium sources (such as tricalcium
phosphate, hydroxyapatite, calcium sulfate, or the like), antimicrobials,
antivirals, vitamins, x-ray opacifiers, or other such materials.

[0051] The bone graft material may be engineered with fibers having
varying resorption rates. The resorption rate of a fiber is determined or
controlled by its material composition and by its diameter. The material
composition may result in a slow reacting vs. faster reacting product.
Similarly, smaller diameter fibers can resorb faster than larger diameter
fibers. Also, the overall porosity of the material can affect resorption
rate. Materials possessing a higher porosity mean there is less material
for cells to remove. Conversely, materials possessing a lower porosity
mean cells have to do more work, and resorption is slower. Accordingly,
the bone graft material may contain fibers that have the appropriate
material composition as well as diameter for optimal performance. A
combination of different fibers may be included in the material in order
to achieve the desired result.

[0052] As with the bioactive glass fibers, the inclusion of bioactive
glass particles can be accomplished using particles having a wide range
of sizes or configurations to include roughened surfaces, very large
surface areas, and the like. For example, particles may be tailored to
include interior lumens with perforations to permit exposure of the
surface of the particles interior. Such particles would be more quickly
absorbed, allowing a tailored material characterized by differential
resorbability. The perforated or porous particles could be characterized
by uniform diameters or uniform perforation sizes, for example. The
porosity provided by the particles may be viewed as a secondary range of
porosity accorded the bone graft material or the implant formed from the
bone graft material. By varying the size, transverse diameter, surface
texture, and configurations of the bioactive glass fibers and particles,
if included, the manufacturer has the ability to provide a bioactive
glass bone graft material with selectively variable characteristics that
can greatly affect the function of the material before and after it is
implanted in a patient. The nano and macro sized pores provide superb
fluid soak and hold capacity, which enhances the bioactivity and
accordingly the repair process.

[0053] FIGS. 1A and 1B illustrate a first embodiment bioactive fibrous
scaffold 10 according to the present disclosure. The scaffold 10 is made
up of a plurality of interlocking fibers 15 defining a three-dimensional
porous support scaffold or matrix 10. The support matrix 10 is made up of
bioactive glass fibers 10 that are interlocked or interwoven, not
necessarily fused at their intersections 17. At least some of the fibers
15 may thus move over one another with some degree of freedom, yielding a
support web 10 that is dynamic in nature. The composition of the fibers
15 used as the struts 19 of the resulting dynamic fibrous scaffold 10 are
typically bioactive glass, ceramic or glass-ceramic formulations, such
that within the range of fiber diameter and construct size, that the
scaffolding fibers 15 are generally characterized as having the
attributes of bioactivity.

[0054] The diameters of the fibers 15 defining the dynamic scaffold 10 are
typically sufficiently small to allow for inherent interlocking of the
resulting three-dimensional scaffold 10 upon itself, without the need for
sintering, fusing or otherwise attaching the fibers 15 at their
intersections 17, although some such fusing or attachment may be employed
to further stiffen the scaffold 10 if desired. Hence the scaffold 10 is
self constrained to not completely fall apart, yet the individual fibers
15 defining the support struts 19 are free to move small distances over
each other to grant the scaffold 10 its dynamic qualities such that it
remains flexible while offering sufficient support for tissue formation
and growth thereupon. In addition, the availability of nano sized fibers
can significantly enhance the surface area available for cell attachment
and reactivity.

[0055] As will be described in detail below, pluralities of fibers 15
characterized as substantially having diameters below 1 micrometer (1000
nanometers) are sufficient to form dynamic scaffolding 10, as are
pluralities of fibers 15 characterized as substantially having diameters
below 100 nanometers. The scaffolding 10 may also be constructed from a
plurality of fibers 15 having multi-modal diameter distributions, wherein
combinations of diameters may be employed to yield specific combinations
of dynamic flexibility, structural support, internal void size, void
distribution, compressibility, dissolution and resorption rates, and the
like. For example, some of the fibers 15 may be fast reacting and resorb
quickly into bone to induce initial bone growth. In addition, some
remnant materials of the bone graft material, such as other fibers 15 or
particulates, may be designed to resorb over a more extended time and
continue to support bone growth after the previously resorbed material
has gone. This type of layered or staged resorption can be critically
important in cases where the surgical site has not sufficiently healed
after the first burst of bone growth activity. By providing varying
levels of resorption to occur, the material allows greater control over
the healing process and avoids the "all or none" situation.

[0056] Typically, the ranges of fiber diameters within a construct range
starting from the nano level, where a nano fiber is defined as a fiber
with a diameter less than 1 micron (submicron), up to about 100 microns;
more typically, fiber diameters range from about 0.005 microns to about
10 microns; still more typically, fiber diameters range from about 0.05
to about 6 microns; yet more typically, fiber diameters range from 0.5 to
about 20 microns; still more typically, fiber diameters range from about
1 micron to about 6 microns. In all cases, predetermined amounts of
larger fibers may be added to vary one or more of the properties of the
resultant scaffolding 10 as desired. It should be noted that as the
amount of smaller (typically less than 10 micrometer) diameter fibers 15
decreases and more of the scaffolding construct 10 contains fibers 15 of
relatively greater diameters, the entire construct 10 typically tends to
become less self constrained. Thus, by varying the relative diameters and
aspect ratios of constituent fibers 15 the resulting scaffold structure
10 may be tailored to have more or less flexibility and less or more
load-bearing rigidity. Furthermore, fibers 15 may be constructed at a
particular size, such as at a nano scale of magnitude, to enhance the
surface area available for cell attachment and reactivity. In one
embodiment, the bone graft material includes at least one nanofiber. In
one embodiment, the bone graft material includes at least one nanofiber.

[0057] One factor influencing the mechanism of a dynamic scaffold 10 is
the incorporation of relatively small diameter fibers 15 and the
resulting implant 20. Porous, fibrous scaffolds 10 may be made by a
variety of methods resulting in an interlocking, entangled, orientated
three-dimensional fiber implant 20.

[0058] As illustrated in FIGS. 1A and 1B, these fibers 15 are not
necessarily continuous, but may be short and discrete, or some
combination of long, continuous fibers 15 and short, discrete fibers 15.
The fibers 15 touch to define intersections 17 and also define pores or
voids 37. By varying the fiber dimensions and interaction modes, the
porosity of the resulting implant, as well as its pore size distribution,
may be controlled. This enables control of total porosity of the implant
(up to about 95% or even higher) as well as control of pore size and
distribution, allowing for materials made with predetermined nano-(pore
diameters less than about 1 micron and as small as 100 nanometers or even
smaller), micro-(pore diameters between about 1 and about 10 microns),
meso-(pore diameters between about 10 and about 100 microns), and
macro-(pore diameters in excess of about 100 microns and as large as 1 mm
or even larger) porosity. The pores 37 typically range in size from about
100 nanometers to about 1 mm, with the pore size and size distribution a
function of the selected fiber size range and size distribution, as well
as of the selected forming technique. However, it is understood that the
fiber and pore size is not limited to these ranges, and while the
description focuses on the nanofibers and nanopores, it is well
understood that the bone graft material of the present disclosure may
equally include macro sized fibers and pores to create range of diameters
of fibers and pores.

[0059] An example of the effect of one distribution of pore size within an
exemplary implant 20 and its volumetric contribution and surface area
contribution is shown with reference to FIGS. 8A and 8B, which are
further described below. The resulting implant or device 20 may thus be a
nonwoven fabric made via a spunlaid or spun blown process, a melt blown
process, a wet laid matt or `glass tissue` process, or the like and may
be formed to have the characteristics of a felt, a gauze, a cotton ball,
cotton candy, or the like.

[0060] Typically, macro-, meso-, and microporosity occur simultaneously in
the device 20 and, more typically, are interconnected. It is unnecessary
here to excessively quantify each type of porosity, as those skilled in
the art can easily characterize porosity using various techniques, such
as mercury intrusion porosimetry, helium pycnometry, scanning electron
microscopy and the like. While the presence of more than a handful of
pores within the requisite size range is needed in order to characterize
a device 20 as having a substantial degree of that particular type of
porosity, no specific number or percentage is called for. Rather, a
qualitative evaluation by one skilled in the art shall be used to
determine macro-, meso-, micro-, and/or nanoporosity. In some
embodiments, the overall porosity of the porous, fibrous implants 20 will
be relatively high, as measured by pore volume and typically expressed as
a percentage. Zero percent pore volume refers to a fully or theoretically
dense material. In other words, a material with zero porosity has no
pores at all. Likewise, one hundred percent pore volume would designate
"all pores" or air. One skilled in the art will be versed in the concept
of pore volume and will readily be able to calculate and apply it.

[0061] Bone graft implants 20 typically have pore volumes in excess of
about 30%, and more typically may have pore volumes in excess of 50% or
60% may also be routinely attainable. In some embodiments, scaffolding
implants 20 may have pore volumes of at least about 70%, while other
embodiments may typically have pore volumes in excess of about 75% or
even 80%. Bone graft implants may even be prepared having pore volumes
greater than about 90%-97%.

[0062] It is advantageous for some bone graft implants 20 to have a
porosity gradient that includes macro-, meso-, and microporosity, and in
some cases nanoporosity. The combination of fibers and particulates to
create the appropriate compression resistance and flexibility is retained
when the bone graft implant 20 is wetted. Bone graft implants 20 are also
typically characterized by interconnected porosity, as such is correlated
with increased capillary action and wicking capability. Such bone graft
implants 20 should be capable of rapidly wicking and retaining liquid
materials for sustained release over time.

[0063] The fibers 15 typically have non-fused linkages 35 that provide
subtle flexibility and movement of the scaffolding 10 in response to
changes in its environment, such as physiological fluctuations, cellular
pressure differences, hydrodynamics in a pulsatile healing environment,
and the like. This in vivo environment can and will change over the
course of the healing process, which may last as long as several months
or even longer. The scaffold 10 typically retains its appropriate
supportive characteristics and distribution of pores 37 throughout the
healing process such that the healing mechanisms are not inhibited.
During the healing process, the pores 37 defined by the matrix of
interlocking and tangled fibers 15 may serve to carry biological fluids
and bone-building materials to the site of the new bone growth. The
fluids likewise slowly dissolve fibers 15 made of bioactive glass and the
like, such that the scaffolding 10, and particularly the pores 37,
changes in size and shape in dynamic response to the healing process.

[0064] Scaffolds 10 are typically provided with a sufficiently permeable
three-dimensional microstructure for cells, small molecules, proteins,
physiologic fluids, blood, bone marrow, oxygen and the like to flow
throughout the entire volume of the scaffold 10. Additionally, the
dynamic nature of the scaffold 10 grants it the ability to detect or
respond to the microenvironment and adjust its structure 20 based on
forces and pressure exerted elements within the microenvironment.

[0065] Additionally, scaffolds 10 typically have sufficient
three-dimensional geometries for compliance of the bone graft implant or
device 20 when physically placed into an irregular shaped defect, such as
a void, hole, or tissue plane as are typically found in bone, tissue, or
like physiological site. The devices 20 typically experience some degree
of compaction upon insertion into the defect, while the permeable
characteristics of the scaffolds 10 are maintained. Typically, as with
the placement of any bone void filler, the device 20 remains within 2 mm
of the native tissue in the defect wall.

[0066] Bone graft implants or devices 20 made from the scaffolding 10 can
appear similar to felts, cotton balls, textile fabrics, gauze and the
like. These forms have the ability to wick, attach and contain fluids,
proteins, bone marrow aspirate, cells, as well as to retain these
entities in a significant volume, though not necessarily all in entirety;
for example, if compressed, some fluid may be expulsed from the
structure.

[0067] Another advantage of the bone graft implants or devices 20 is their
ability to modify or blend the dynamic fiber scaffolds 10 with a variety
of carriers or modifiers to improve handling, injectability, placement,
minimally invasive injection, site conformity and retention, and the like
while retaining an equivalent of the `parent` microstructure. Such
carriers ideally modify the macro-scale handling characteristic of the
device 20 while preserving the micro-scale (typically on the order of
less than 100 micrometers) structure of the scaffolding 10. These
carriers resorb rapidly (typically in less than about 2 weeks; more
typically in less than about 2 days) without substantially altering the
form, microstructure, chemistry, and/or bioactivity properties of the
scaffolding. These carriers include polaxamer, glycerol, alkaline oxide
copolymers, bone marrow aspirate, and the like.

[0068] FIG. 2A shows an embodiment of an implant 20 in the form of a strip
or sheet, for example. FIG. 2B shows an embodiment of an implant 20 in
the form of a three-dimensional structure similar to a cotton ball, for
example. In one example, a plurality of interlocking fibers 15 are spun
or blown into a randomly-oriented assemblage 20 having the general
appearance of a cotton ball. The fibers 15 are typically characterized as
having diameters of from less than about 1000 nm (1 micrometer) ranging
up to approximately 10, 000 nm (10 micrometers). The resulting
cotton-ball device 20 may be formed with an uncompressed diameter of
typically from between about 1 and about 6 centimeters, although any
convenient size may be formed, and may be compressible down to between
about 1/2 and 1/4 of its initial size. In some cases, the device 20 can
substantially return to its original size and shape once the compressive
forces are removed (unless it is wetted with fluids, which kind of locks
the device into desired shape and density, or is vacuum compressed).
However, in many cases the device 20 may remain deformed. By varying the
relative diameters of some of the fibers 15, structures ranging from
`cotton ball` to `cotton candy` may be produced, with varying ranges of
fiber diameters from less than about 10 nm to greater than about 10
microns.

[0069] FIG. 2C shows an embodiment of the implant 20 in the form of a
woven mesh or fabric, for example. In one example, fibers 15 may be
woven, knitted, or otherwise formed into a fabric device 20 having a
gauze-like consistency. The fibers 15 are typically greater than 1 about
micrometer in diameters and may be as large as about 100 micrometers in
diameter. The micro-scale orientation of the fibers 15 is typically
random, although the fibers may be somewhat or completely ordered. On a
macro-scale, the fibers 15 are typically more ordered. The constituency
of these devices 20 may have varying amounts of smaller fibers 15
incorporated therein to maintain the self constrained effect.

[0070] FIGS. 3A and 3B illustrate another embodiment of the present
disclosure, a bioactive fibrous scaffold 110 as described above with
respect to FIGS. 1A and 1B, but having glass microspheres or particulate
140 distributed therethrough. The glass particulate 140 is typically made
of the same general composition as the fibers 115, but may alternately be
made of other, different compositions. One advantage of the presence of
particulate 140 in the implant 120 is its contribution to the implant's
120 overall compression resistance. Since one function of the implant 120
is typically to absorb and retain nutrient fluids that feed the regrowth
of bone, it is advantageous for the implant to offer some level of
resistance to compressive forces, such that the liquids are not
prematurely `squeezed out`. Particulate 140, whether spherical or
particulate, stiffens the implant, which is otherwise a porous
scaffolding primarily composed of intertangled fibers 115. The
particulate 140 can act as pillars, lending structural support to the
overall implant 120.

[0071] The glass particulate 140 is typically generally spherical, but may
have other regular or irregular shapes. The glass particulate 140
typically varies in size, having diameters ranging from roughly the width
of the fibers 115 (more typically, the struts 119) to diameters orders of
magnitude greater than the typical fiber widths. Particulate 140 may also
vary in shape, from generally spherical to spheroidal, or elliptical to
irregular shapes, as desired. The particulate 140 may even be formed as
generally flat platelets; further, the platelets (or other shapes) may be
formed having perforations or internal voids, to increase the effective
surface area and dissolution rate. Likewise, the shape of the particulate
140 may be varied to influence such factors as bone cell attachment,
particulate coatability, and the like.

[0072] In one embodiment, the glass particulates 140 may have an average
diameter of about 20 microns to about 1 millimeter. In another
embodiment, the particulates 140 may have an average diameter of about
300 to 500 microns. In still another embodiment, the glass particulates
140 may have an average diameter of about 350 microns.

[0073] As with the fibers, bioactive glass particulate 140 may be coated
with organic acids (such as formic acid, hyaluronic acid, or the like),
mineralogical calcium sources (such as tricalcium phosphate,
hydroxyapatite, calcium sulfate, or the like), antimicrobials,
antivirals, vitamins, x-ray opacifiers, or other such materials. While
smaller particulate may tend to lodge in or around fiber intersections
117, larger particulate tend to become embedded in the scaffolding 120
itself and held in place by webs of fibers 115. Pore-sized microspheres
may tend to lodge in pores 137.

[0074] The glass particulate 140 may be composed of a predetermined
bioactive material and tailored to dissolve over a predetermined period
of time when the scaffolding 110 is placed in vitro, so as to release a
predetermined selection of minerals, bone growth media, and the like at a
predetermined rate. The composition, size and shape of the glass
particulate 140 may be varied to tailor the resorption rate of the
bioactive glass, and thus the rate at which minerals and the like are
introduced into the body (and, likewise, how long the particulate 140 is
available to provide increased compression resistance to the scaffolding
implant 20). For example, for a given bioactive glass composition and
particulate volume, irregularly shaped particulate 140 would have more
surface area than spherical particulate 140, and would thus dissolve more
rapidly.

[0075] Further, the glass particulate 140 may be hollow bioactive glass,
polymer or the like microspheres filled with specific mixture of
medicines, antibiotics, antivirals, vitamins or the like to be released
at and around the bone regrowth site at a predetermined rate and for a
predetermined length of time. The release rate and duration of release
may be functions of particulate size, porosty and wall thickness as well
as the distribution function of the same.

[0076] As discussed above, the shape and texture of the bone graft
material may be randomly configured to maximize its overall volume,
surface area, and pliability or, in stark contrast, can be manufactured
with the bioactive glass fibers in a more rigid and uniform arrangement,
such as, for example in a mesh or matrix type assembly. In a mesh or
matrix assembly, as illustrated by the non-limiting examples shown in
FIGS. 4A to 4C the glass fibers can be arranged in a stacked arrangement
limiting the flexibility in a directional manner, or, the fibers can be
layered wherein alternating layers are in a crossed relationship one to
the other. In FIG. 4A, the matrix assembly 110 is shown having an ordered
configuration with discrete layers comprising fibers 115 and particulate
140. In FIG. 4B, the matrix assembly is shown having a randomly arranged
configuration of fibers 115 and particulate 140 dispersed throughout. In
FIG. 4C, the matrix assembly 110 is shown having a configuration in which
the layers have different porosities due to differences in the spacing of
the fibers 115 and particulate 140 throughout each layer. That is, the
size of the pores 137 varies throughout the matrix assembly due to the
unevenly spaced fibers 115 and particulate 140. It should be understood
that, while FIGS. 4A and 4C show discretely aligned fibers 115 for the
purposes of illustrating the concept herein, the individual layers of
material 110 may include fibers 115 and particulate 140 that are
unorganized and randomly aligned.

[0077] An advantage of the present disclosure is the wide variety of
alternative configurations and structural arrangements that result in an
equally varied functionality of the material being used by a surgeon. As
illustrated in FIGS. 4A-C, the bone graft material of the present
disclosure can include embedded bioactive glass particles within the
bioactive glass fiber construct. The inclusion of such particles, as
determined by the quantity, size, and characteristics of the particles,
can affect the compressibility, bioabsorbability, and porosity of the
resulting bone graft material. Additional additives, such as calcium
phosphates (CaP), calcium sulfates (CaS), hydroxyapatite (HA),
carboxymethycellulose (CMC), collagen, glycerol, gelatin, and the like
can also be included in any of the many varied constructions of the
bioactive glass fiber bone graft material to assist in bone generation
and patient recovery. Such additives may be in the range of 0 to 90
percent porous. Another additive, collagen, may be included and may also
be of the ultraporous kind having a porosity of up to 98 percent.

[0078] In one embodiment, the surface area of the bone graft material is
maximized to increase the bone ingrowth into the structural matrix of the
material. Another useful variable is the capability of the bone graft
material to selectively be composed and configured to provide layers of
varying porosity, such as nano-, micro-, meso-, and micro-porosity, so as
to act as a cell filter controlling the depth of penetration of selected
cells into the material. Because the preparation of the bone graft
material can be selectively varied to include bioactive glass fibers
and/or particles having different cross-sectional diameters, shapes
and/or compositions, the material properties may be tailored to produce a
bone graft material with differential absorption capabilities. This
feature permits the surgeon to select a bone graft material specifically
for the needs of a specific situation or patient. Controlling the pace of
bone ingrowth into the bioactive glass matrix of the material allows the
surgeon to exercise almost unlimited flexibility in selecting the
appropriate bone graft material for an individual patient's specific
needs.

[0079] In another embodiment, the bioactive glass was formulated with
strontium partially replacing calcium. The partial replacement of calcium
with strontium yields a bioactive glass with a reduced
resorption/reaction rate and also with an increased radiodensity or
radioopacity. Thus, the bioactive glass stays present in the body for a
longer period of time and also presents a more readily visible x-ray
target.

[0080] In another embodiment, silver (or other antimicrobial materials)
may be incorporated into the bioactive glass fiber scaffolding structural
matrix. Silver is an antimicrobial material, and enhances the inherent
antimicrobial properties of the bioactive glass material. Typically,
silver is added as a dopant to very fine bioactive glass fibers, such
that the silver is quickly released as the very fine fibers dissolve at
the implant site, allowing the silver to act as an anti-microbial agent
to prevent infection immediately after surgery while the remaining
scaffolding material does its work. Alternately, Ag may be introduced as
fibers and interwoven with the bioactive glass fibers, as particles
similar to the glass particulate discussed above, or the like. Of course,
varying the composition of the bioactive glass from which the fibers are
formed to create an alkaline (high pH in the range of 8-10) glass may
also provide the material with antimicrobial properties. Other properties
and features of the material of the present disclosure are described in a
co-pending and commonly owned U.S. patent application Ser. No. ______,
entitled "DYNAMIC BIOACTIVE BONE GRAFT MATERIAL AND METHOD OF USE," filed
Oct. 28, 2010, the disclosure of which is hereby incorporated by
reference.

[0081] One advantage of the graft material of the current disclosure is
that it is dynamic, and can be easily molded into various shapes or form,
without losing the essential structure and porosity. By packaging the
material in a functional tray, where the tray acts as a mold, the
material can be provided in various shapes in the operating room. In
particular, the material becomes a cohesive mass when a fluid such as
blood, saline, bone marrow, other natural body fluids, etc. is added.

[0082] In an embodiment, as shown in FIGS. 5A to 5C, the bone graft
material is provided as part of a surgical kit 200. The kit 200 includes
a tray portion 210 having a recess or well 212, and more typically a set
of nested recesses, for storing, holding and manipulating the bone graft
material 10, 110, and a lid portion 220 for sealingly engaging the tray
portion 210. The tray and lid portions 210, 220 are typically formed from
thermoplastic materials, but may alternately be made of any convenient
material. The deepest recess chamber 212 typically has a simple geometry,
such as a rectangular block or wedge shape, such that the so-loaded bone
graft material likewise has a simple geometry.

[0083] The bone graft material 10, 110 is typically provided as an
intertangled or interwoven mass of bioactive glass fibers. The bioactive
glass fibers may be provided in format that is ready to be surgically
emplaced in a bony cavity (such as a woven or mesh format), or may be
provided in a format that requires additional preparation prior to
emplacement (such as a more loosely intertangled format) that requires
the addition of a liquid, such as saline, glycerol, gelatin, plasma, or
collagen gel or chips, to assist in rendering the mass of bioactive glass
more pliable and structurally unitary. Such liquids may optionally be
included in the kit packaging 200, or provided separately.

[0084] In one example, a kit 200 is provided, including a tray body 210
and a lid 200 engagable with the tray body. The tray body 210 includes
one or more recesses 212 for containing a volume of bioactive glass
fibers 10. The volume of bioactive glass fibers may be woven, knitted,
intertangled or provided as a loose stack. The volume of bioactive glass
fibers may optionally include fibers of other compositions, such as
antimicrobial silver, polymers, or alternate glass compositions, and may
also optionally include particulate matter or particulate of the same
bioactive glass composition, or alternate compositions such as alternate
glass, metal, metal oxide, medicinal, nutritive, and/or antimicrobial or
the like. The kit may also optionally include a liquid, such as saline or
collagen gel, for mixing with the bioactive glass volume.

[0085] In operation, the surgeon removes the lid 220 of the kit 200 and
removes a portion of the included bioactive glass material 10. The
bioactive glass material may then be shaped and sized by the surgeon for
insertion into a bony cavity. This process may involve the addition of an
appropriate liquid to the bioactive glass material, such as saline,
collagen gel, plasma, blood, or the like, to achieve a desired degree of
pliability and/or structural integrity. Once the bioactive glass material
is sized and shaped as desired, it is inserted into the bony cavity. This
process may be done as a single operation or as a series of steps.

[0086] FIGS. 6A to 6D illustrate additional embodiments of a mold tray
that may form a part of the surgical kit. As in the previous embodiment,
the mold trays may comprise a base component and a lid component
configured to fit onto the base component to form an enclosed container.
Each of the trays may be provided with a fluid port. More than one fluid
port may be provided on a tray. The fluid ports allow filling of the
material as well as access to introduce a fluid or wetting agent as
previously described to the material. Further, while the present
embodiments show mold trays that have a single lid portion, it is
understood that multiple lids may be provided for use with a single tray
portion. Alternatively, a tray portion may be used without a lid portion.
For example, the tray portion may include either one side that is open or
the tray portion may be a hollow shell with at least one port to allow
filling of the material and introduction of the fluid or wetting agent.

[0087] The mold tray may be sterile. In addition, the base component and
lid component form an enclosed container when attached together. The lid
component may further include tabs for ease of handling. Each of the base
and lid components have corresponding depressed or raised portions to
form a predefined molded shape or well. The base component may have more
than one preformed well for creating a shaped mold. That shape may be,
for example, a rectangle, square, disc, crescent, star, wave, diamond,
C-shape, W-shape, S-shape, or T-shape, as shown in FIGS. 6B-6D. Further,
the predefined molded shape may have rounded edges to create a smooth
implant. Alternatively, the predefined molded shape may have a tapered
leading edge for ease of implantation. The molded tray may also be
disposable.

[0088] An exemplary kit 300 is shown in FIG. 6A having a mold tray 310
that allows a lid similar to 220 to be snap-fitted on the tray 310. The
mold tray 310 may include a well 312 as well as a fluid port 330. These
fluid ports 330 may also serve as finger depressions or finger rests, in
order to further facilitate handling. The tray 310 may further include a
tab 340 for additional ease of handling. Another exemplary kit 400 is
shown in FIG. 6B having a mold tray 410 containing dual wells, 412a and
412b, along with a fluid port 430. The dual wells allow more than one
implant 20 to be created with the same mold tray 410.

[0089] FIG. 6C illustrates another exemplary embodiment of a surgical kit
500 of the present disclosure. The kit 500 may include a mold tray 510
having two wells 512a, 512b for creating two shaped implants 20. Fluid
ports 530 may be provided for ease of introducing a wetting agent to the
fibrous material. FIG. 6D shows yet another exemplary embodiment of a
surgical kit 600 of the present disclosure having a mold tray 610 with a
shaped well 612 and including a plurality of fluid ports 630 surrounding
the well 612.

[0090] There are clinical advantages to providing a surgical kit of the
present disclosure. For instance, a closed system comprising the mold
tray with its corresponding tray and lid portions allows the user to keep
the graft material cohesive. Further, the system allows for hands-free
operation in the sense that there is no contact with the graft material
until it is ready to be used for surgery. This reduces the chances of
infection, since the mold tray may also serve as a protective container
for the graft material and prevent handling prior to use.

[0091] Another advantage of the system of the present disclosure is that
the user can control the porosity of the graft material by controlling
the weight of the fibrous material added. Since the density of the base
material is known, as is the volume of the tray cavity, the overall
porosity of the graft material inside the ray can be precisely calculated
and controlled. Furthermore, the system allows the user to customize the
graft material and create, for example, a graft material with multiple
porosity regions. Such a material can be produced by adding a layer of
material of one porosity into a tray, then adding a material of a
different porosity onto that first layer. Subsequent layers or materials
of different porosities may be added as needed to create a composite of
desired porosities. Likewise, various materials may be added sequentially
to create a stacked or layered composite of multiple materials. Thus, it
is possible to create a material composition having different materials
and different porosity gradients or regions throughout the composition.

[0092] There are a number of ways to form the final molded or shaped
product. For example, a force may be applied to the lid(s) to compress or
squeeze the fibrous material into the well(s) of the tray to create the
desired shape. The force applied may be from manual pressure, or from
vacuum pressure. Or, the force may be simply of filling the mold tray
with the material. In one embodiment, the applied force compresses the
porous, fibrous composition. The composition may remain compressed after
the force has been removed.

[0093] An exemplary method for loading and shaping the fibrous material 10
is illustrated in FIGS. 7A-7L. FIG. 7A shows a loading container 710 and
lid 720 for receiving the ultraporous, fibrous graft material 10 of the
present disclosure. The lid 720 may be configured for sliding engagement
with the container 710, as shown in FIG. 7B. Of course, it is understood
that the lid 720 and container 710 may be configured in other ways to
allow easy opening and removal, such as for example, snap-fitted
engagement, hinged engagement or other frictional engagements as is known
in the art. The fibrous graft material 10 may be loaded inside the closed
container 710 as shown in FIG. 7C, and compressed inside the container
710 such as with a machine press 730 or other type of press.

[0094] After the fibrous material 10 is loaded inside the container 710,
the material can be transferred to the mold tray 310 of a surgical kit,
as shown in FIG. 7D. A base frame 740 may be provided having an opening
sufficiently sized and shaped for receiving the container 710, while the
frame 740 itself can be configured to seat onto the mold tray 310. As
shown in FIGS. 7D and 7E, the base frame 740 may be seated inside one of
the recesses formed in the mold tray 310, and allow the container 710
loaded with the fibrous material 10 to be securely placed over the
implant well of the mold tray. The container 710 is placed onto the base
frame 740 with the open end facing towards the mold tray 310, such that
removal of the lid 720 exposes the loaded fibrous material 10 as shown in
FIG. 7F.

[0095] To compress the fibrous material 10 in the container 710 into the
well of the mold tray 310, a hand press 750 may be provided. The hand
press 750 may be sized and shaped to fit neatly within the container 710,
as shown in FIG. 7G. Removal of the hand press 750 reveals a partially
compressed and shaped fibrous material 10, as illustrated in FIG. 7H. At
this stage, additional compression may be performed on the material 10
inside the mold tray 310. For example, as FIGS. 7I-7K show, further
compression may be effected by hand pressing using the press 750 with the
container 710 removed to avoid any encumbrances, leaving only the base
frame 70 behind. The press 750 may be the same size and shape as the
previous one, or it may have a different size or shape similar to the
desired final product. As shown in FIG. 7L, the final product may be a
fibrous material 10 suitably compressed into one of the wells in the mold
tray 310 and is now ready for clinical use.

[0096] In some cases, it may be desirable to partially compress the graft
material and then transfer the partially compressed graft material into
the tray for further and final shaping. In other instances, it may simply
be desirable to compress the graft material with a specialized mold or
fixture and then shape the compressed material using the mold tray. For
instance, the ultra porous fibrous graft material may be machine pressed
prior to transferring to the mold tray. Alternatively, it is also
possible to provide a hand press and tray that fits over the mold tray,
such that you can utilize the hand press to compress the ultra porous
fibrous graft material into the mold tray without the use of a lid.
Accordingly, the steps provided in FIGS. 7A-7L may be used in a variety
of combinations to achieve the desired shape while also providing maximum
convenience to the user.

[0097] In most cases, the deepest recess chamber of the mold tray or press
mold typically has a simple geometry, such as a rectangular block or
wedge shape, such that the so-loaded bone graft material likewise has a
simple geometry. The bone graft material is typically provided as an
intertangled or interwoven mass of bioactive glass fibers. The bioactive
glass fibers may be provided in format that is ready to be surgically
emplaced in a bony cavity (such as a woven or mesh format), or may be
provided in a format that requires additional preparation prior to
emplacement (such as a more loosely intertangled format) that requires
the addition of a liquid, such as saline, glycerol, gelatin, plasma, or
collagen gel or chips, to assist in rendering the mass of bioactive glass
more pliable and structurally unitary. Such liquids may optionally be
included in the kit packaging, or provided separately.

[0098] In operation, the surgeon removes the lid of the kit and removes a
portion of the included bioactive glass material. The bioactive glass
material may then be shaped and sized by the surgeon for insertion into a
bony cavity. This process may involve the addition of an appropriate
wetting agent or liquid to the bioactive glass material, such as saline,
collagen gel, plasma, naturally occurring fluid such as blood, or the
like, to achieve a desired degree of pliability and/or structural
integrity. Another suitable wetting agent or liquid may also include a
bonding agent or glue, such as a bioresorbable glue like carboxyl methyl
cellulose (CMC) solution. The wetting agent can also serve as a setting
material that enhances the mechanical (and thus clinical handling)
properties of the graft material. For example, use of a physiologic
setting agent like blood or bone marrow aspirate, where clotting can
occur over time (for example, in the range of about 10-15 minutes), can
lead to better physical properties of the mixer. Once the bioactive glass
material is sized and shaped as desired, it is inserted into the bony
cavity. This process may be done as a single operation or as a series of
steps.

[0099] The bone graft material 10, 110 is typically provided as an
intertangled or interwoven mass of bioactive glass fibers. The bioactive
glass fibers may be provided in format that is ready to be surgically
emplaced in a bony cavity (such as a woven or mesh format), or may be
provided in a format that requires additional preparation prior to
emplacement (such as a more loosely intertangled format) that requires
the addition of a liquid, such as saline, glycerol, gelatin, plasma, or
collagen gel or chips, to assist in rendering the mass of bioactive glass
more pliable and structurally unitary. Such liquids may optionally be
included in the kit packaging 200, or provided separately.

[0100] Although the bone graft material of the present disclosure is
described for use in bone grafting, it is contemplated that the graft
material of the present disclosure may also be applied to soft tissue or
cartilage repair as well. Accordingly, the application of the fibrous
graft material provided herein may include many different medical uses,
and especially where new connective tissue formation is desired.

[0101] While the present disclosure has been illustrated and described in
detail in the drawings and foregoing description, the same is to be
considered as illustrative and not restrictive in character. It is
understood that the embodiments have been shown and described in the
foregoing specification in satisfaction of the best mode and enablement
requirements. It is understood that one of ordinary skill in the art
could readily make a nigh-infinite number of insubstantial changes and
modifications to the above-described embodiments and that it would be
impractical to attempt to describe all such embodiment variations in the
present specification. Accordingly, it is understood that all changes and
modifications that come within the spirit of the present disclosure are
desired to be protected.